Department of Psychology, Memorial University of Newfoundland, St. John's, Canada.
Behavioural Neurobiology Laboratory, Centre for Addiction and Mental Health, Toronto, Canada.
J Psychopharmacol. 2021 Aug;35(8):1003-1016. doi: 10.1177/02698811211000765. Epub 2021 Apr 28.
Antidepressant drugs in adolescent depression are sometimes mired by efficacy issues and paradoxical effects. Transcranial direct current stimulation (tDCS) could represent an alternative.
AIMS/METHODS: We tested the antidepressant action of prefrontal tDCS and paroxetine (20 mg/kg, intraperitoneal) in olfactory bulbectomised (OBX) adolescent rats. Using enzyme-linked immunosorbent assays and in situ hybridisation, we examined treatment-induced changes in plasma brain-derived neurotrophic factor (BDNF) and brain serotonin transporter (SERT) and 5-HT-1A mRNA.
OBX-induced anhedonia-like reductions in sucrose preference (SP) correlated with open field (OF) hyperactivity. These were accompanied by decreased zif268 mRNA in the piriform/amygdalopiriform transition area, and increased zif268 mRNA in the hypothalamus. Acute paroxetine (2 days) led to a profound SP reduction, an effect blocked by combined tDCS-paroxetine administration. Chronic (14 days) tDCS attenuated hyperlocomotion and its combination with paroxetine blocked OBX-induced SP reduction. Correlations among BDNF, SP and hyperlocomotion scores were altered by OBX but were normalised by tDCS-paroxetine co-treatment. In the brain, paroxetine increased zif268 mRNA in the hippocampal CA1 subregion and decreased it in the claustrum. This effect was blocked by tDCS co-administration, which also increased zif268 in CA2. tDCS-paroxetine co-treatment had variable effects on 5-HT1A receptors and SERT mRNA. 5-HT1A receptor changes were found exclusively within depression-related parahippocampal/hippocampal subregions, and SERT changes within fear/defensive response-modulating brainstem circuits.
These findings point towards potential synergistic efficacies of tDCS and paroxetine in the OBX model of adolescent depression via mechanisms associated with altered expression of BDNF, 5-HT1A, SERT and zif268 in discrete corticolimbic areas.
抗抑郁药在青少年抑郁症中的应用有时会受到疗效问题和矛盾作用的困扰。经颅直流电刺激（tDCS）可能是一种替代方法。
目的/方法：我们测试了前额叶 tDCS 和帕罗西汀（20mg/kg，腹腔内注射）对嗅球切除术（OBX）青少年大鼠的抗抑郁作用。使用酶联免疫吸附试验和原位杂交技术，我们研究了治疗引起的血浆脑源性神经营养因子（BDNF）和脑 5-羟色胺转运体（SERT）和 5-HT-1A mRNA 的变化。
OBX 引起的快感缺失样蔗糖偏好（SP）减少与旷场（OF）过度活跃相关。这些变化伴随着梨状皮层/杏仁核过渡区中zif268 mRNA 的减少，以及下丘脑 zif268 mRNA 的增加。急性帕罗西汀（2 天）导致 SP 显著减少，这种作用被联合 tDCS-帕罗西汀给药阻断。慢性（14 天）tDCS 减弱了过度运动，其与帕罗西汀联合阻断了 OBX 引起的 SP 减少。BDNF、SP 和过度运动评分之间的相关性在 OBX 后发生改变，但通过 tDCS-帕罗西汀联合治疗得到了正常化。在大脑中，帕罗西汀增加了海马 CA1 亚区的 zif268 mRNA，减少了屏状核的 zif268 mRNA。这种作用被联合 tDCS 给药阻断，tDCS 还增加了 CA2 中的 zif268。tDCS-帕罗西汀联合治疗对 5-HT1A 受体和 SERT mRNA 有不同的影响。5-HT1A 受体的变化仅发生在与抑郁相关的海马旁/海马亚区，而 SERT 的变化发生在恐惧/防御反应调节脑干回路中。
这些发现表明，tDCS 和帕罗西汀在 OBX 青少年抑郁症模型中可能具有协同疗效，其机制与 BDNF、5-HT1A、SERT 和 zif268 在离散的皮质边缘区表达的改变有关。
